This proposal addresses a simple question: what are the molecular mechanisms that underlie naturally occurring variation in plant responses to the environment? Among the best-studied plant signaling pathways are those that mediate the effects of ambient light, along with those that integrate light information with other variables to control flowering. Despite considerable efforts using forward and reverse genetics as well as the tools of functional genomics, there remain many gaps in our knowledge of the genes involved in light signaling and flowering responses. Therefore, we propose a combination of genetic and genomic approaches to identify genes that vary between natural isolates of Arabidopsis thaliana, and whose variation leads to strain-specific differences in light signal transduction and flowering responses. We have already demonstrated the feasibility of such studies by identifying naturally occurring functional variants in several genes. In addition, we have generated a large set of resources that enable the proposed studies. Specifically, we propose to (1) identify additional genomic regions controlling light signaling and flowering; (2) fine-map and identify genes underlying natural variation; (3) perform detailed mechanistic analyses of the identified genes and their natural variants; and (4) to conduct species-wide studies of these natural variants as well as of other candidates affecting natural variation. Importantly, we also expect to gain new basic insights into light and flowering responses. In support of this assertion, we have already identified two genomic regions that affect a seedling's response to light, but do not contain any gene known from laboratory mutagenesis experiments to control this process. We have strong preliminary evidence that at least one of the regions contains a change-of-function allele whose effect on light-regulated development would not have been predicted from the knockout phenotype of the affected gene. The proposed work will thus expand both our mechanistic knowledge of light and flowering responses, and our understanding of naturally occurring genetic variation in A. thaliana. These studies will set the stage for future, larger-scale investigations.